Field of the Invention
This invention relates to the P21 protein and conjugates and compositions comprising the P21 protein. These products are particularly useful in the treatment of cancer.
Background Information
Cancer is one of the major causes of human mortality and has been the subject of intensive research. It is well known that almost all malignant tumours result from the transformation of a single cell into an immortal state, where the cell has lost the ability to control proliferation.
Uncontrolled proliferation results from a malfunction in the control of the cell cycle which, in eukarya, is controlled largely by cyclins and cyclin-dependent kinases (CDKs). A complex mechanism of control over the phosphorylation state of the cyclins and CDKs controls whether cyclin/CDK complexes are able to drive the cell into the next phase of the cycle. The importance of the phosphorylation state of cyclin/CDK complexes is reflected by the fact that a large number of cancers involve mutations in the P53 and P21 tumour suppressor proteins, which are key components in the control of cyclin/CDK phosphorylation and complex formation. In particular, P21 blocks cycD/cdk4 complex formation and causes G1 arrest. Reviews detailing the P21 protein and its biological function may be found in O'Reilly M A, Antioxid Redox Signal. 2005 January-February; 7(1-2):108-18 and Liu G & Lozano G, Cancer 25 Cell. 2005 February; 7(2):113-4.
The treatment of cancer usually involves a combination of surgical procedures, radiotherapy and chemotherapy (including immunotherapy). Despite significant advances in cancer therapies in recent years, there remains a constant need for the development of improved therapies. Ideally, a cancer therapy will specifically target and destroy cancerous cells only.
A further problem that needs to be addressed is drug resistance resulting from chemotherapy. The continued administration of a cytotoxic drug can cause a tumour, that was initially sensitive to the drug, to become increasingly drug resistant such that the drug loses its therapeutic efficacy. Methods of improving the sensitivity of cancerous cells to drugs are therefore also required.